BACKGROUND: Hair follicles undergo cycles of repeated growth and regression. The Wnt pathway plays an important role in the regeneration and differentiation of hair follicles. Sfrp2, a Wnt inhibitor, is involved in the developmental and disease processes of various cells and tissues by modulating the Wnt pathway. OBJECTIVE: The aim of this study was to understand the role of Sfrp2 in hair follicles through investigation of the Sfrp2 expression pattern in the skin and its effect on keratinocytes. METHODS: We investigated Sfrp2 mRNA expression and the expression of the wnt target genes, Ccnd1 and C-myc, at various mouse hair follicle developmental stages using Real-time polymerase chain reaction. We also investigated the effect of SFRP2 on the proliferation and differentiation of mouse keratinocyte cells by adding SFRP2 protein or overexpressing Sfrp2 using an in vitro culture system. RESULTS: Sfrp2 expression peaked in the catagen phase and remained high until telogen, and then declined at the beginning of the next anagen. An inverse relationship to Sfrp2 expression was found for the expression of the Wnt target genes, C-myc and Ccnd1. In addition, we also observed inhibited proliferation of mouse keratinocytes in the presence of SFRP2. CONCLUSION: These results suggest that Sfrp2 may play a role in the catagen phase by inhibiting the proliferation of keratinocyte and functioning as a Wnt inhibitor in keratinocytes.
Animals ; Genes, myc ; Hair Follicle* ; Hair* ; Keratinocytes* ; Mice ; Real-Time Polymerase Chain Reaction ; Regeneration ; RNA, Messenger ; Skin ; Wnt Signaling Pathway

In order to elucidate in vivo neuronal cell death in the retina, and involvement of NF-kappa B in this process, we studied the degeneration of retinal ganglion cells (RGCs) and the activation of NF-kappa B after transection of the optic nerve of adult rat at 5 mm from the eyeball. The morphology of dying ganglion cells in the retinal ganglion cell layer was observed by light and electron microscopy, the activation of NF-kappa B was investigated immunohistochemically. Seven and 14 days post-axotomy, dying cells contained pyknotic nuclei. The death of retinal ganglion cells involved apoptosis, activation of NF-kappa B (p50 and p65) was prominent in a time dependent manner. We observed axotomy-induced NF-kappa B activation, which may mediate apoptosis of retinal ganglion cells.
Animal ; Apoptosis/physiology ; Axotomy ; Immunohistochemistry ; Male ; Microscopy, Electron ; NF-kappa B/biosynthesis* ; Optic Nerve/surgery ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/ultrastructure ; Retinal Ganglion Cells/pathology* ; Retinal Ganglion Cells/metabolism ; Substances: NF-kappa B

PURPOSE: The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans. MATERIALS AND METHODS: To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects. RESULTS: Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4+/-0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant. CONCLUSION: We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.
Alleles ; Asian Continental Ancestry Group/*genetics ; Blood Pressure/*genetics ; Case-Control Studies ; Diastole/genetics ; Female ; Gene Frequency ; *Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Hypertension/*genetics/*physiopathology ; Luciferases/metabolism ; Middle Aged ; Polymorphism, Single Nucleotide/*genetics ; Promoter Regions, Genetic/genetics ; Renin/*genetics ; Republic of Korea ; Risk Factors ; Systole/genetics ; Transfection

Symptomatic epidural varix presenting with radiculopathy is extremely rare. The most common misdiagnosis is reported as a sequestrated prolapsed nucleus pulposus in the preoperative evaluation. The method of evaluating enhanced MRI studies improved the efficacy of discovery and treatment of this condition. We experienced 6 cases of epidural varices that were diagnosed with T1 fat suppressed post-gadolinium enhanced MRI studies and we present the operative findings.
Diagnostic Errors ; Magnetic Resonance Imaging* ; Radiculopathy ; Varicose Veins*

To examine the protection of retinal cell death by glutamate antagonists in vivo, this study was carried out in pressure-induced ischemia model. Firstly, we observed that ischemia resulted in the similar retinaldamage to the injuries caused by NMAD and Kainate toxicity. Secondly, the retinal cell death caused by ischemia was prevented by MK801 and CNQX, glutamate antagonists for NMDA and Kainate excitotoxicity, respectively at 24hr after ischemia. MK801 was shown to prevent the cell death in ganglion cell layer and CNQX in inner unclear layer. In addition, the combination of CNQX and MK801 protected the retina neuronal cell from ischemic injury better than when they were applied separately. The partial protection of retinal cell death by glutamate antagonists in ischemia model indicates that glutamate eoxicity as well as other cell death mechanism such as apoptosis mediates ischemia induced retinal cell death. Thus, cell death by other mechanism must be also blocked in order to prevent retinal cell death, completely.
6-Cyano-7-nitroquinoxaline-2,3-dione* ; Apoptosis ; Cell Death ; Dizocilpine Maleate* ; Excitatory Amino Acid Antagonists ; Ganglion Cysts ; Glutamic Acid ; Ischemia* ; Kainic Acid* ; N-Methylaspartate* ; Neurons ; Retina ; Retinaldehyde*

The Hairless (HR) gene regulates the expression of several target genes as a transcriptional corepressor of nuclear receptors. The hair follicle (HF), a small independent organ of the skin, resides in the epidermis and undergoes regenerative cycling for normal hair formation. HF development requires many genes and signaling pathways to function properly in time and space, one of them being the HR gene. Various mutations of the HR gene have been reported to cause the hair loss phenotype in rodents and humans. In recent studies, it has been suggested that the HR gene is a critical player in the regulation of the hair cycle and, thus, HF development. Furthermore, the HR gene is associated with the Wnt signaling pathway, which regulates roliferation and differentiation of cells and plays an essential role in hair and skin development. In this review, we summarize the mutations responsible for human hair disorders and discuss the roles of the HR gene in HF development.
Epidermis ; Hair ; Hair Follicle ; Humans ; Phenotype ; Receptors, Cytoplasmic and Nuclear ; Rodentia ; Skin ; Wnt Signaling Pathway

Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval in ECG and manifests predisposition to life threatening arrhythmia which often leads to sudden cardiac death. We encountered a 3-generation family with 5 affected family members in which LQTS was inherited in autosomal dominant manner. The LQTS is considered an ion channel disorder in which the type and location of the genetic mutation determines to a large extent the expression of the clinical syndrome. Upon screening of the genomic sequences of cardiac potassium ion channel genes, we found a single nucleotide C deletion mutation in the exon 3 of KCNH2 gene that co-segregates with the LQTS in this family. This mutation presumably resulted in a frameshift mutation, P151fs+15X. This study added a new genetic cause to the pool of mutations that lead to defected potassium ion channels in the heart.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/*genetics ; DNA Mutational Analysis ; Ether-A-Go-Go Potassium Channels/*genetics ; Exons ; Female ; Frameshift Mutation ; Genotype ; Humans ; Long QT Syndrome/*diagnosis/genetics ; Male ; Middle Aged ; Pedigree ; Republic of Korea ; Sequence Deletion

During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5′ untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5′ UTR IRES activity and an increase in HR protein expression without changing mRNA levels. We also found that this regulation was disrupted in a mutant Hr 5′ UTR that has a mutation responsible for Marie Unna hereditary hypotrichosis (MUHH) in both mice and humans. These findings suggest that Hr mRNA expression is regulated at the post-transcriptional level via IRES-mediated translation control through interaction with PCPB2, but not in MUHH.

BACKGROUND AND OBJECTIVES: The renin-angiotensin system (RAS) genes have been studied extensively as etiologic essential hypertension (EH) candidate genes in human populations worldwide. The angiotensin I-converting enzyme (ACE) plays an important role in the RAS for the regulation of blood pressure. Recent reports on the association of ACE gene polymorphisms with EH and the related cardiovascular diseases have been controversial. Therefore, this study investigated the association of three polymorphisms (I/D, G14480C and A22982G) in the ACE gene with EH in Koreans. SUBJECTS AND METHODS: This study recruited a sample population of 887 Koreans (comprising of 461 controls and 426 EH cases) from Cardiovascular Genome Center in Korea. The ACE gene polymorphisms were determined by a polymerase chain reaction and a SNP-IT assay. RESULTS: The genotype and the allele frequencies of all three polymorphisms in the hypertensives and the normotensives not significantly different (p>0.05). In the female control group, there was a significant difference in SBP among the genotype with the I/D polymorphism (p<0.05). There was also an association between the ACE polymorphisms and the hypertensive male group with the total cholesterol level. Haplotype analysis showed that none of the haplotypes were significantly associated with hypertension. CONCLUSION: ACE polymorphisms do not appear to have any apparent association with essential hypertension in Koreans, who have a more homogeneous genetic structure than other ethnic groups.
Asian Continental Ancestry Group ; Blood Pressure ; Cardiovascular Diseases ; Cholesterol ; Ethnic Groups ; Female ; Gene Frequency ; Genetic Structures ; Genome ; Genotype ; Haplotypes ; Humans ; Hypertension* ; Korea ; Male ; Peptidyl-Dipeptidase A ; Polymerase Chain Reaction ; Renin-Angiotensin System

Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.
Carcinoma, Hepatocellular ; Cell Line ; Cell Survival ; Clone Cells ; Doxorubicin ; Drug Resistance ; Dual Specificity Phosphatase 6* ; Dual-Specificity Phosphatases* ; Ectopic Gene Expression ; Fluorouracil* ; Humans ; Lentivirus ; MicroRNAs